A challenge to medicine since its inception has been the development of methods that permit rapid and accurate detection of diseases. Despite advances in diagnostic technology over the years, the current techniques for the diagnosis of many diseases are either inadequate or cost prohibitive for wide scale application. One such disease is bladder cancer.
As a worldwide problem, it was estimated that there are 50,900 new cases of bladder cancer per year in Western Europe, 3,700 in Japan and 34,000 in North America (WHO 1984), with at least 3 to 4 times this number of patients attending hospitals for follow-up or treatment. Bladder cancer affects about three times as many men as women. It is the fourth most common form of cancer in men and the ninth most common in women in the United States. Over 90% of bladder cancers are of the transitional cell type (transitional cell carcinoma or "TCC").
Bladder cancer may present in several ways, according to the stage when discovered. A diagnosis of TCC of the bladder or urinary tract structures is staged and graded, according to the following system, based on biopsy or surgical specimen results.
______________________________________ Stages of Primary Bladder Cancer Stage of Primary Bladder Tumor Description ______________________________________ Tis (Cis) Tumor in situ (carcinoma in situ); flat tumor Ta Superficial (noninvasive) papillary tumor which does not infiltrate beyond the basement membrane or superficial mucosa T1 Tumor which infiltrates the lamina propria muscularis mucosa (or submucosa) T2 Tumor which invades the superficial muscle (muscularis propria) T3 Tumor which invades the deep muscle or perivesical fat T4 Tumor which invades any of the following: the prostate, vagina, uterus, pelvic wall, or abdominal wall ______________________________________
The tumor grade is based on the degree of anaplasia, or loss of cell differentiation.
______________________________________ Grades of Primary Bladder Cancer Grade of Primary Bladder Tumor Description ______________________________________ Grade I (low) Slight anaplasia Grade 11 (medium) Moderate anaplasia Grade Ill (high) Severe anaplasia ______________________________________
Bladder cancer occurs in two major forms: superficial (Tis, Ta, T1) and invasive (.gtoreq.T2). Superficial tumors may have variable grade, with higher grade superficial tumors having poorer prognosis. About 70% of superficial tumors will develop one or several recurrences during a five-year follow-up period. The major risk is that the tumor will become invasive. Most invasive tumors are subsequently manifested as high grade as well as stage.
The invasive form of bladder cancer accounts for approximately 20%-30% of all bladder cancer. Invasive bladder cancer starts in the mucosa lining the bladder, invades through the basement membrane to reach muscle wall, and finally the pelvic tissues and surrounding organs, including local lymph nodes. The outlook depends on the stage and grade, with five-year survivals from 11%-60%. The treatment is by radiotherapy, chemotherapy and surgery.
Patients with invasive bladder tumors are monitored by urine cytology and check cystoscopy. Although cytology is a non-invasive and less difficult procedure, it can be prone to error or uncertainty. For example, a positive result by cytology may be helpful, but a negative result cannot be taken as evidence of the absence of a tumor. Further, the reporting varies greatly with the cytologist's experience. Cystoscopy is an invasive, expensive and occasionally hazardous procedure, as it is frequently carried out under anesthesia. Despite the uncertainties associated with cystoscopic checks, they are nevertheless still considered by many medical practitioners as the diagnostic tool of choice because of the absence of better tests.
Malignancies that are low stage-superficial or noninvasive (Ta, Tis, T1)-respond to endoscopic therapy. Yet, as noted above, recurrence at the same or another site in the bladder is relatively common. Depending on the stage and grade of the superficial tumor, progression to an invasive (.gtoreq.T2) tumor may occur. Since invasive lesions respond poorly to endoscopic therapy and the treatment of choice is cystectomy, it is therefore of critical importance to be able to monitor all patients with a confirmed diagnosis of bladder cancer in order to detect disease recurrence and/or progression.
Thus, there is a need in the art for a method of determining the invasiveness of a bladder cancer. The present invention fulfills these needs and further provides other related advantages.